COVID-19 has changed and so has our immunity. Here’s how to think about risk from the virus now

By Brenda Goodman, CNN

(CNN) — COVID-19 was never just another cold. We knew it was going to stick around and keep changing to try to get the upper hand on our immune systems.

But we’ve changed, too. Our B cells and T cells, keepers of our immune memories, aren’t as blind to this virus as they were when we first encountered the novel coronavirus in 2020. The US Centers for Disease Control and Prevention has screened blood samples and estimates that 97% of people in the US have some immunity to COVID-19 through vaccination, infection or both.

Then there’s science: We have updated vaccines and good antivirals to lean on when cases start to rise. Masks still work. Rapid tests are in stores. We now know to filter the air and to ventilate our spaces.

Those strategies, plus our hard-won immunity, had helped bring our national numbers of infections, hospitalizations and deaths down to levels that felt almost forgettable.

Almost.

Now that COVID-19 infections have started to rise again, it feels like people all over the country are testing positive, and it’s hard to know how to react. The government has been dialing back its response since the end of the public health emergency in May. Good COVID-19 data is hard to come by and harder to interpret.

So if people are less likely to be hospitalized or die from a COVID-19 infection now, has the danger passed? Is there still reason to worry if you do catch the infection for a second, third or fourth time?

Experts say it’s less risky to catch COVID-19 than it used to be, but there are still good reasons not to treat it casually.

“At this point, the risk is lower because of our prior immunity, whether for severe outcomes or for long COVID,” said Dr. Megan Ranney, an emergency physician and dean of the Yale School of Public Health.

“COVID is still more dangerous than the flu, but its level of danger is becoming less,” she said, noting that we’re still very early in our human experience with the coronavirus, even four years in, and there are still things we don’t know.

“But for it to behave like other respiratory viruses in terms of seasonality and surges is entirely expected,” she added.

It would be “really weird” for COVID to disappear or for it not to cause illnesses, hospitalizations and deaths. “It is still a virus,” Ranney said.

But a somewhat predictable waxing and waning of infections doesn’t make COVID-19 something to turn our backs on.

Our immune systems are better at spotting danger

After more than three grueling years, nearly all Americans have some immunity against COVID-19.

That means our immune systems – as long as they’re healthy and working as they should – will remember most forms of the coronavirus when it next comes our way.

That process takes some time to get going, however. That lag may give the virus enough of a window to get a foothold in our nasal passages or lungs, and we get sick. We may feel crummy for a few days, but then our B cells and T cells get their antibody production up and running. Eventually, they shut the virus down, and we get better.

That’s what should happen. But for many, their immune system just doesn’t kick in as quickly or as vigorously as it should.

Immune function drops off naturally with age. About 1 in 4 Americans is over the age of 60, according to census data. Then there are certain medications and health conditions that suppress immune function. About 3% of the U.S. population – 7 million people – is severely immunocompromised, according to the National Institutes of Health. This is a group taking medications to protect organ transplants or who are getting powerful drugs for cancer treatment, for example.

Then there’s individual variability. Through genetic bad luck, some people may just be at higher risk of serious reactions to COVID-19 infections, and they probably wouldn’t know it.

Taken together, that’s a sizeable pool of people who benefit greatly from having antibodies at the ready to take on the coronavirus as fast as possible. Vaccines get those antibodies in place and ready to work as soon as they’re needed.

Sometimes, people are so immunocompromised that vaccines can’t help them much, either. They benefit from preventive shots containing COVID-fighting antibodies that are built to stick around the body for a few months. Until this year, there was such a preventive product available, Evusheld. But the virus has evolved so much that Evusheld lost its potency, and in January, the FDA revoked its authorization.

Since then, people who have very low immune function haven’t had anything to protect them from infection or severe disease. But that could change. The government announced this week that it’s funding the development of a new preventive antibody through the drug company Regeneron. Trials of that drug are expected to start this fall, according to the US Department of Health and Human Services.

While nearly all of us have immune systems that can recognize key parts of the virus now, even that memory to the infection fades over time. The longer it has been since you’ve been infected or vaccinated, the more forgetful your immune system becomes.

Those B cells and T cells, “they’re going to be a little slower to respond. They’re not they’re not as primed and ready to go,” Ranney said.

Your strongest immunity will be in the two weeks to two months after you get your vaccines. That means it’s smart to try to get your shots shortly before COVID is expected to be on the upswing. Just like for flu, experts expect the worst of COVID to hit in the fall and winter.

CDC Director Dr. Mandy Cohen said that even though cases are going up now, most people will be better off waiting a few weeks to get the newly updated COVID-19 vaccines rather than trying to get one of the older bivalent vaccines right now. But this is dependent on personal risk, so if you’re concerned, talk to your doctor or nurse practitioner about your options.

Risks from new variants

Variants are another reason people need to keep getting COVID vaccines. The coronavirus evolves constantly. Most of the time, its improvements are incremental. In essence, it slips on a hat or fake mustache, but that’s not enough to completely disguise it from our immune system or our vaccines when it tries to break in.

Occasionally, it gets a makeover. It has cut and dyed its hair, had plastic surgery and lost a ton of weight, so to speak. These big changes make it unrecognizable to our immune system and sometimes to vaccines and drugs we use to fend it off.

That happened during the first wave of Omicron. A virus emerged in South Africa and Botswana that was wholly different from the viruses in circulation but still caused COVID-19. It quickly spread worldwide, infecting vaccinated and previously infected people alike. Omicron caused a jaw-dropping 1 million infections a day in the United States in the winter of 2021.

Another virus like that has emerged on the world stage. It’s called BA.2.86, and it has more than 30 amino acid changes to its spike protein, which makes it as genetically distant from its next closest ancestor – BA.2 – as the original Omicron variant was from the ancestral strain of the SARS-CoV-2 virus that emerged in 2019 in China.

Compared with the very first sequences of the virus that causes COVID-19, it has 58 changes to amino acids in its spike protein, according to Dr. Jesse Bloom, who studies the molecular structure of viruses at the Fred Hutchinson Cancer Center in Seattle.

It’s not clear exactly where BA.2.86 came from. Scientists believe that the pattern of mutations it carries are characteristic of a virus that’s been changing inside the body of a chronically infected person. Typically, these patients have diminished immune function so that they can’t completely clear the virus from their bodies, but they have enough immunity that it puts pressure on the virus to keep changing to survive. Or it may have previously circulated in a part of the world with limited variant surveillance.

Scientists have spotted 13 human infections with this emerging variant have been confirmed from six countries: Israel, Denmark, the United Kingdom, the United States, Portugal and South Africa. The status of the patients is not known in every case. Of the cases for which information on the patients is available, one has been hospitalized, and none have died.

The people do not appear to have had contact with each other, and only one has traveled, indicating that the variant is present around the world and spreading in the community – though it is not known to what extent.

It has also been picked up at very low levels in wastewater in the US, Switzerland, Denmark and Thailand.

It is also not clear whether this virus will outcompete other circulating variants and grow to cause widespread infections. Variant hunters around the world seem to have spotted it early.

Researchers are studying whether it will be able to evade immunity from past infection and vaccination. More information should be available within a few weeks.

Unfortunately, the fact that the new coronavirus can morph this way means we’ll probably need to keep updating our vaccines and our immunity to keep pace.

The US government has launched Project NextGen, which aims to create longer-lasting and more variant-proof vaccines. The first clinical trials of those new vaccines are expected to start this winter, HHS says.

Lasting risks like long COVID

Dr. Daniel Griffin, an infectious disease specialist at Columbia University, says people with COVID worry about three things: “ ‘Am I going to die? Am I going to end up in the hospital?’ But for most people, it’s ‘Am I going to be sick and stay sick for many months? Am I going to get long COVID?’ ”

“And for most people, actually, that’s the most significant risk.”

Experts noted that there isn’t a lot of good research on the risk of getting long COVID now.

Based on the science we do have, they say the risk of long-term complications appears to be going down.

There were fewer post-COVID conditions reported by patients after Omicron infections compared with those infected during the Delta wave, according to a recent study posted ahead of peer review.

But it seems the risk is not entirely gone.

Another recent study out of Australia, of nearly 23,000 people with confirmed COVID-19 infections between July and August 2022, found that 18% of the more than 11,000 who responded met the case definition for long COVID. Researchers defined it as any new or continuing symptoms more than 90 days after a COVID-19 infection.

It was a highly vaccinated group, too. More than 94% of people who responded to the survey had gotten at least three doses of a COVID-19 vaccine. In this study, women, those between the ages of 50 and 69, people who lived in rural areas and those with fewer vaccine doses were more likely to report having long COVID. The study was posted as a preprint ahead of peer review by outside experts.

Based on his experience treating long COVID patients, Griffin said that the percentage reported in the Australian paper seems high. After people are vaccinated, their risk of getting long COVID drops from about 10% to 20% to the single digits, he said. It goes down even further, he said, if they use antivirals like Paxlovid.

“The general principles are, the sicker you are, the more naive you are immunologically, the higher the chance of acute and chronic complications, and that’s kind of going by multiple studies showing that generally earlier in the pandemic, with the original variants, people had more acute and chronic complications,” said Dr. Peter Chin-Hong, an infectious disease specialist at the University of California at San Francisco.

Chin-Hong said recent studies do seem to show that the overall proportion of infections that result in problems like long COVID seems to be dropping over time.

“When you look at studies, long COVID is going down by one-half, and there have been multiple studies like in the UK, the US Census Bureau and all that stuff with the different variants” showing this, he said.

Risks from reinfection

It seems like there’s always a “but” with COVID-19, and here it is: Across the population, the risk of chronic complications from an infection may be going down, but each infection also adds to the chances that a person may face lasting damage. A recent study published in the journal Nature Medicine found that reinfections are not benign. Each additional infection increased a person’s risk of death, hospitalization and other long-term problems.

A recent National Institutes of Health-funded study that combed through millions of patient records to find people who had both first and second COVID-19 infections backs up those findings.

Among more than 300,000 people with reinfections, researchers found that the risk of having a more severe disease was slightly higher the second time around. That research was also posted as a preprint ahead of peer review.

Study author Dr. Nathaniel Hendrix, a researcher and data scientist with the American Board of Family Medicine, said he set out to disprove the findings of the Nature Medicine study, which was based on an older group of mostly male patients treated through the Veterans Affairs health system. Some critics felt this population couldn’t be representative of the larger US. After He said he was surprised when his own study found that the risk of more severe illness did not drop at all for people getting COVID-19 a second time.

Hendrix said it’s made him think twice about taking precautions.

“I think it’s still worthwhile to do what you can to avoid getting infected,” he said.

COVID risks for kids

This overall reduction in post-COVID consequences for patients appears to apply to kids, too.

Earlier in the pandemic, pediatric infectious disease specialists were on the lookout for a rare complication of COVID-19 infection in kids called multisystem inflammatory syndrome in children, or MIS-C.

MIS-C starts two to six weeks after a COVID-19 infection. It can cause an ongoing fever as well as more than one of the following symptoms: stomach pain, bloodshot eyes, diarrhea, dizziness, skin rash or vomiting, according to the CDC. MIS-C can be serious, but most kids get better with medical care.

A study published earlier this year found that for every 100 children hospitalized with COVID-19 in 2021, there were 17 MIS-C hospitalizations, and some cases were fatal.

Recent studies suggest that both the number and the severity of MIS-C cases has gone down globally over time. Studies have shown that vaccination cuts the risk even further, by more than 90%.

“Now, the risk is about 6 percent with Omicron at least by one study, and so about half” of where it once was, Chin-Hong said.

Fortunately, the risk of long-term problems after COVID-19 has gone down, Griffin said, but for many, it hasn’t gone away.

He recently saw a young long COVID patient who started to cry because she’s been sick for more than two years, and she doesn’t seem to be getting better.

COVID still seems to be unique in its ability to cause extended illness this way. Griffin says it’s possible for people who get influenza to get a problem known as long flu, but the proportion of people who wind up with that is about 1%. With COVID, right now, Griffin thinks that number is at least 5%.

That’s a big enough risk that Dr. Kristin Englund, an infectious disease specialist at the Cleveland Clinic in Ohio, says it shouldn’t be dismissed.

“Even a mild case of COVID may result in symptoms that last for weeks or four months or longer than that, so it is not something that I would take lightly,” she said.

How to stay safe

The pandemic was a kind of crash course in how to deal with contagious respiratory viruses. Experts say the protective measures we adopted then should probably be part of how we live now.

It’s still important to break out masks in crowded, poorly ventilated spaces when infections are rampant and to use rapid tests when you get sick so you know whether you might need to take antivirals. Everyone can benefit from vaccines and antivirals, but those are particularly important if you’re high risk: people over age 60, those who are pregnant, and those who have underlying health conditions or take medication that reduces their immunity.

“Those things haven’t changed in the past year,” Ranney said. “It’s just that we all thought this was done. And so now we’re having to re-remember what we did last fall to help manage the virus.”

Dr. Ellie Murray, an epidemiologist at the Boston University School of Public Health, says we should treat COVID at least as seriously as we do the flu: “not just chicken soup but time off, bed rest, fluids and reduced contact with others while sick, plus vaccination and good hygiene to prevent infection.”

Murray notes that we used to think that there was nothing more we could do about the flu and that the level of annual deaths was the lowest it was going to get. The pandemic proved otherwise. “We can have fewer flu deaths, and decreasing those is easier even than decreasing COVID deaths,” she said.

“So a better approach would be to treat both the flu and COVID as a new normal, which includes all the things we used to do for the flu but also adds in ventilation, masking, testing and treatment. These additions will help reduce the burden of disease for both COVID and the flu.”

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